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Sunday, February 20, 2011

Neoplasia

Neoplasia literally means "new growth.“

Sir Willis’s definition of Neoplasia :

"an abnormal mass of tissue the growth of which exceeds and is uncoordinated with that of the normal tissues and persists in the same excessive manner after the cessation of the stimuli which evoked the change."

Malignant, as applied to a neoplasm, implies that the lesion can invade and destroy adjacent structures and spread to distant sites (metastasize)

All tumors have 2 components

1) the parenchyma, made up of transformed or neoplastic cells, a tumor derives ite name from it and

The natural history of malignant tumors can be divided into four phases;

Transformation

Growth of transformed cells

Local invasion

Distant metastases

Differentiation and Anaplasia

The differentiation of parenchymal cells refers to the extent to which they resemble their normal forebears morphologically and functionally

Anaplasia : lack of differentiation

Benign neoplasms are composed of well-differentiated cells that closely resemble their normal counterparts. A lipoma is made up of mature fat cells laden with cytoplasmic lipid vacuoles, and a chondroma is made up of mature cartilage cells that synthesize their usual cartilaginous matrix

Malignant neoplams - grow much faster, eventually spreading locally and to distant sites (metastasizing) and causing death. Rapidly growing malignant tumors often contain central areas of ischemic necrosis because the tumor blood supply, derived from the host, fails to keep pace with the oxygen needs of the expanding mass of cells

The rate of growth of a tumor is determined by three factors:

The doubling time of tumor cells

The fraction of tumor cells that are in replicative pool

The rate at which cells are shed and lost in the growing lesion

rapidly growing tumors tend to be poorly differentiated

some cancers (particularly choriocarcinomas) may disappear spontaneously as they become totally necrotic, leaving only secondary metastatic implants

Invasion

A benign neoplasm remains localized at its site of origin. It does not have the capacity to infiltrate, invade, or metastasize to distant sites, as do malignant neoplasms

as fibromas and adenomas slowly expand, most develop an enclosing fibrous capsule

the leiomyoma of the uterus is discretely demarcated from the surrounding smooth muscle by a zone of compressed and attenuated normal myometrium, but there is no well-developed capsule

Cancers grow by progressive infiltration, invasion, destruction, and penetration of the surrounding tissue. They do not develop well-defined capsules

Metastasis

development of secondary implants (metastases) discontinuous with the primary tumor, in remote tissues

basal cell carcinomas of the skin and most primary tumors of the central nervous system that are highly invasive in their primary sites of origin but rarely metastasize

the more anaplastic and the larger the primary neoplasm, the more likely is metastatic spread

Different ways of metastasis of tumor

Spread by seeding

cancers of the ovary, which often cover the peritoneal surfaces widely

medulloblastoma or ependymoma, may penetrate the cerebral ventricles and be carried by the cerebrospinal fluid to reimplant on the meningeal surfaces

Lymphatic spread

is more typical of carcinomas, whereas hematogenous spread is favored by sarcomas

Carcinoma of the breast usually arises in the upper outer quadrant and first spreads to the axillary nodes

skip metastases

ultimately to reach the vascular compartment via the thoracic duct

"sentinal lymph node" is defined as the first lymph node in a regional lymphatic basin that receives lymph flow from a primary tumor. It can be delineated by injection of blue dyes

Hematogenous spread

Since all portal area drainage flows to the liver, and all caval blood flows to the lungs, the liver and lungs are the most frequently involved secondary sites in hematogenous dissemination

Cancers arising near the vertebral column often embolize through the paravertebral plexus

carcinomas of the thyroid and prostate

Renal cell carcinoma often invades the renal vein to grow in a snakelike fashion up the inferior vena cava, sometimes reaching the right side of the heart.

Epidemiology of cancer

Environment and geographical considerations

breast cancer are about fourfold to fivefold higher in the United States and Europe compared with Japan. Conversely, the death rate for stomach carcinoma in men and women is about seven times higher in Japan than in the United States

Age:

the frequency of cancer increases with age. Most cancer mortality occurs between ages 55 and 75

Childhood retinoblastoma is the most striking example of this category. Approximately 40% of retinoblastomas are familial

Familial adenomatous polyposis is another hereditary disorder marked by an extraordinarily high risk of cancer. Innumerable polypoid adenomas of the colon, and virtually 100% of patients develop a carcinoma of the colon by age 50

Familial cancer syndrome: no clear pattern of transmission

Features that characterize familial cancers include early age at onset, tumors arising in two or more close relatives of the index case, and sometimes multiple or bilateral tumors

Carcinogenesis is a multistep process at both the phenotypic and the genetic levels, resulting from the accumulation of multiple mutations

tumor progression and associated heterogeneity most likely result from multiple mutations that accumulate independently in different cells, generating subclones with different characteristics, such as ability to invade, rate of growth, metastatic ability, karyotype, hormonal responsiveness, and susceptibility to anti-neoplastic drugs

Even though most malignant tumors are monoclonal in origin, by the time they become clinically evident, their constituent cells are extremely heterogeneous